Progress in Alzheimer's disease research in the last year

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with a prevalence of 5 % after 65 years of age, increasing to about 30 % in people aged 85 years or older. It is characterized by progressive cognitive impairment, including impaired judgment, decision-making and orientation, and in some cases accompanied by psycho behavioral disturbances or language impairment. Herein, we summarize and discuss the main articles describing novel findings in AD published over the last year, including clinical, therapeutic, and research issues. \ua9 2013 Springer-Verlag Berlin Heidelberg

"Somos los descamisados": a representação do peronismo nascente na mídia impressa porteña (1945-1946)

O presente trabalho tem como objetivo compreender as diferentes formas de representação da classe trabalhadora argentina, politizada através do nascente movimento peronista, pelo principal jornal de grande circulação da capital nesse período, o jornal La Nación. Leva-se em conta que, por buscar a representação de um processo histórico e não a concretude do mesmo, o trabalho está na intersecção entre a história política argentina e a história da mídia, compreendendo que – de acordo com Capelato (1988) – a mídia, ao representar uma realidade, também atua para conformá-la. A hipótese inicial levantada é a de que o jornal La Nación tem uma visão racista e preconceituosa dos trabalhadores peronistas, entendendo que a relação entre eles e o então coronel Juan Domingo Perón era uma relação verticalizada de obediência e devoção. A conotação racista se dá pela clivagem, na representação, entre trabalhadores imigrantes supostamente democráticos e trabalhadores de ascendência indígena migrando das províncias do norte da Argentina, propensos, de acordo com o jornal, a barbárie, tese essa utilizada posteriormente pela historiografia conservadora. O recorte temporal se dá entre outubro de 1945 e fevereiro de 1946, tendo como marco inicial as manifestações multitudinárias que libertaram Perón da prisão e como marco final sua eleição como presidente da Argentina.El presente trabajo tiene por objetivo comprender las múltiples maneras de representar la clase trabajadora de la Argentina en el proceso de toma de conciencia fruto del naciente movimiento peronista, por medio del principal medio de comunicación impresa del período en la capital, el diario La Nación. Teniendo en cuenta que, por buscar la representación de un proceso histórico y no la concretud del mismo, el trabajo está en la intersección de la historia política argentina y la historia de los medios. También teniendo en cuenta que - según Capelato (1988) - los medios, al representar una realidad, también actúan para conformarla. La hipótesis inicial planteada es la de que el diario La Nación tiene una visión racista y prejuiciosa de los trabajadores peronistas, comprendiendo que la relación entre ellos y el entonces coronel Juan Domingo Perón era una relación verticalizada de obediencia y de devoción. La connotación racista se explica por el clivaje, en la representación, entre trabajadores con un supuesto perfil democrático, provenientes de las olas inmigratorias y trabajadores de ascendencia indígena provenientes de las provincias del norte de la Argentina y propensos, según el diario, a la barbarie, tesis que fue utilizada a posteriori por la historiografía conservadora. El recorte temporal se da en el período entre octubre de 1945 y febrero de 1946, teniendo como marco inicial las multitudinarias manifestaciones que liberaron de la cárcel a Perón y como marco final su elección como presidente de la Argentina

An emerging role for long non-coding RNA dysregulation in neurological disorders

A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered. \ua9 2013 by the authors; licensee MDPI, Basel, Switzerland

Role of Genetics and Epigenetics in the Pathogenesis of Alzheimer's Disease and Frontotemporal Dementia

Alzheimer's disease (AD) and frontotemporal dementia (FTD) represent the first cause of dementia in senile and pre-senile population, respectively. A percentage of cases have a genetic cause, inherited with an autosomal dominant pattern of transmission. The majority of cases, however, derive from complex interactions between a number of genetic and environmental factors. Gene variants may act as risk or protective factors. Their combination with a variety of environmental exposures may result in increased susceptibility to these diseases or may influence their course. The scenario is even more complicated considering the effect of epigenetics, which encompasses mechanisms able to alter the expression of genes without altering the DNA sequence. In this review, an overview of the current genetic and epigenetic progresses in AD and FTD will be provided, with particular focus on 1) causative genes, 2) genetic risk factors and disease modifiers, and 3) epigenetics, including methylation, non-coding RNAs and chromatin remodeling

IL-33 and its decoy sST2 in patients with Alzheimer's disease and mild cognitive impairment

BACKGROUND: Interleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer's disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHOD: IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1\u3b2 and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro A\u3b242-stimulated monocytes of AD, MCI, and HC individuals was examined. RESULTS: As compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1\u3b2 concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+A\u3b2 42-stimulated monocytes downregulated IL-1\u3b2 generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+A\u3b242-stimulated monocytes of HC alone. CONCLUSIONS: These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI

Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule.

Sulfatides have been established recently as ligands for L-selectin, and we investigated whether they trigger transmembrane signals through ligation of L-selectin. We found that sulfatides trigger the increase of cytosolic free calcium in neutrophils and that this effect was strictly dependent on sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory. Chymotrypsin and phorbol 12-myristate 13-acetate treatment of neutrophils caused shedding of L-selectin, but not of class I major histocompatibility complex antigens or beta 2 integrins, and blunted the capability of neutrophils to respond to sulfatides with an increase of cytosolic free calcium. Four different anti-L-selectin antibodies (DREG-200, LAM1/3, LAM1/6, and LAM1/10), but not four control antibodies directed against different surface molecules of neutrophils, also triggered an increase of cytosolic free calcium. The anti-L-selectin antibodies were stimulatory both if used in a soluble form, after cross-linking with anti-mouse F(ab')2 fragments, and immobilized to protein A of Staphylococcus aureus through the Fc fragment. With immobilized antibodies, an increase of cytosolic free calcium was found also by plating neutrophils on antibodies bound to protein A-coated coverslips and monitoring the increase of cytosolic free calcium by fluorescence microscopy. Both sulfatides and anti-L-selectin antibody effects were not inhibited by pertussis toxin, thus indicating that a pertussis toxin-sensitive GTP-binding protein was not involved in signal transduction. Sulfatides also triggered an increase of tumor necrosis factor-alpha and interleukin-8 mRNAs in neutrophils. Also to act as stimuli of cytokine mRNA expression, sulfatides required sulfation of the galactose ring, as non-sulfated galactocerebrosides were not stimulatory, and depended on expression of L-selectin, as shedding of this molecules induced by chymotrypsin blunted their effects. These findings suggest that L-selectin can transduce signals activating selective cell function